1-(2,6,6-trimethylcyclohex-2-en-1-yl)but-2-en-1-one (α-damascone) is a aroma substance that is found in a variety of essential oils. Due to its characteristic organoleptic properties, α-damascone is of great commercial interest as fragrance or as flavor. In particular, α-damascone is widely used as fragrance chemical in deodorants and perfumes.
Today, the vast majority of the demanded α- or β-damascone, respectively, is produced synthetically from unsaturated aldehydes or ketones, e.g. from citral, cyclocitral or cyclogeranic acid, which are available in large amounts from natural and/or petrochemical sources.
There is a demand for novel processes that allow the efficient production of 1-(2,6,6-trimethylcyclohex-2-en-1-yl)but-2-en-1-one (α-damascone), e.g. by making use of mild reaction conditions to improve the yield and reduce the formation of unwanted by-products.
The synthesis of α-damascone was frequently described in the art.
DE1807568 for instance describes, besides the synthesis of other compounds, a process for the synthesis of 1-(2,6,6-trimethylcyclohex-2-en-1-yl)but-2-en-1-one (α-damascone) starting from 3,7-Dimethylocta-2,6-dienal (citral) mainly through two different routes. Route 1 comprises the reaction of α-cyclocitral (2,6,6-trimethylcaclohex-2-ene-1-carbaldehyde), obtained via the cyclization of citral, with 1-propenylmagnesiumbromide to the alcohol (E)-1-(2,6,6-trimethylcyclohex-2-en-1-yl)but-2-en-1-ol, which is then oxidized to α-damascone using chromium trioxide or manganese dioxide. Route 2 comprises the reaction of citral with 1-propenylmagnesiumbromide to 6,10-dimethyl-2,5,9-trien-4-ol, which is oxidized with manganese dioxide to the corresponding ketone 6,10-dimethyl-2,5,9-trien-4-one (pseudo damascone). The pseudo damascone is then cyclized to α-damascone using boron trifluoride diethyl etherate. For the oxidation of the alcohol intermediates to the corresponding ketones, silver acetate, oxygen containing derivatives of transition metal elements, in particular chromium trioxide, manganese dioxide or permangenate, and gaseous molecular oxygen are mentioned as suitable oxidizing agents.
Nakatani et al., Agr. Biol. Chem., 1974, Vol. 38(7), pp. 1351-1354, describe a process for the synthesis of α-damascone starting from citral, which first comprises the reaction of citral with allylmagnesium bromide to the alcohol 6,10-dimethyl-2,5,10-trien-4-ol, which is oxidized with chromium trioxide in the presence of pyridine or 3,5-dimethyl pyrazole to the corresponding ketone 6,10-dimethyl-2,5,10-trien-4-one. This ketone is then isomerized with potassium tert-butanolate to 6,10-dimethyl-2,5,9-trien-4-one (pseudo damascone). The thus obtained pseudo-damascone is finally cyclized to α-damascone using a mineral acid, in particular phosphoric acid, or a lewis acid, in particular tin tetrachloride.
The iron catalyzed aerobic oxidation of allylic alcohols is also described in the art.
Liu et al., Org. Lett., 2013, Vol. 15, pp. 5150-5153, describe the oxidation of several allylic alcohols, such as geraniol or (E)-4-methylhept-4-ene-3-ol, with molecular oxygen in the presence of catalytic amounts of Fe(NO3)3, (2,2,6,6-Tetramethylpiperidin-1-yl)oxyl (TEMPO) and NaCl.
The vast majority of the known synthetic processes, which aim for the synthesis of α-damascone from citral, proceed via the formation of allylic alcohol intermediates, which are oxidized to the corresponding ketones. The oxidation of these allylic alcohol intermediates typically suffer from low yiels, due to the formation of side products, when strong oxidants, such as chromium trioxide or potassium permanganate, are used and/or suffer from long reaction times, in particular if mild oxidants, such as manganese dioxide or molecular oxygen, are applied. Furthermore, these processes often require an additional isomerization step in order to arrive at the desired α-damascone, which further lowers the overall yield.
Due to the unsatisfactory overall yields, these processes are unsuitable for the effective production of α-damascone from citral, in particular for technical scale production.